In vivo studies indicate that renin release is controlled by three intrarenal mechanisms-the baroreceptor, macula densa and beta-adrenoreceptors. Much evidence supports the concept that prostaglandin I2 serves as extracellular mediator linking activation of baroreceptor or macula densa to renin release by juxtaglomerular cells. Similarly, norepinephrine serves as extracellular mediator linking activation of beta adrenoreceptor to renin release by juxtaglomerular cells. Since both prostaglandin I2 and beta adrenoreceptor agonists can stimulate release of renin by juxtaglomerular cells, and since adenosine is inhibitory, we propose that cyclic adenosine monophosphate serves as the intracellular mediator. The use of a number of substances which either stimulate or inhibit renin and cyclic adenosine monophosphate production in juxtaglomerular cells (eg. prostaglandin I2, isoproterenol, 9-substituted adenosine derivatives, phosphodiesterase inhibitors, protein kinase inhibitors) will be used to test our hypothesis. Data on renin release and cyclic adenosine monophosphate production as determined by radioimmunoassay on a cell culture system enriched in juxtaglomerular cells will be evaluated.